What makes a plenary session different from the other sessions here? I don’t know.

10:00-11:30 Session 6: Plenary Session (Chair: Marian Waterman [UC Irvine])

  10:00-10:30 Wei Yan (Univ. of Nevada) “The control of cytoplasm removal during late spermiogenesis”

I produced 100,000 sperm in the time it took him to say his first sentence. I’m so proud.

Part of process of spermiogenesis is removal of cytoplasm and organelles from sperm. Found late expression of Spem1 protein in maturation process which doesn’t affect sperm numbers, but mulls strongly affect motility and sperm head morphology. They have a membranous bag bending the head. Can still produce progeny through ICSI.

  10:30-11:00 Anne Calof (UC Irvine) “Feedback, proliferation, and fate in sensory epithelium development”

All about regulation of olfactory epithelium, a proliferative neural tissue.
GDF8 aka myostatin regulates muscle proliferation. Related GDF11 is neural homolog. Where is it acting in olfactory lineages? GDF11 induces cell cycle withdrawal; GDF11 mutants have thicker olfactory epi, more actively dividing cells.

Different in retinal epithelium, where it doesn’t change proliferation, but changes relative numbers of different cel types in retina.

In olfactory epithelium, GDF11 doesn’t affect morphology either. 

  11:00-11:30 Jerry Crabtree (Stanford) “Instructive roles of ATP chromatin remodeling in early development and reprogramming”

Brg/Brm ATP dependent complexes that remodel chromatin. 13 subunits & 27 genes, 12 times larger than a nucleosome; combinatorial assembly. Brg important for activation of Oct4 in ICM and repression in TE — combinatorial properties allow different functions in different tissues. Context dependent sensitivity allows for a lot of different functions.

Someone remind me that I definitely need to read up more on these complexes…man, there are a lot of complications and permutations here.

Hey, it’s all about evolution. This is the session labeled as being about evo-devo, but I’ve been thinking about evolution in all of the talks, so I guess here we’re just making it more explicit.

08:00-09:30 Session 5: Evolution of Development (Chair: Elaine Seaver [Univ. Hawaii])

  08:00-08:30 Brad Davidson (Univ. of Arizona) “Microenvironmental cues refine inductive signaling during Ciona intestinalis heart development”

Ciona heart is a simple system: only two precursors! Inductive response to FGF is dependent on cell adhesion. Cool confocal work on cell behavior.

  08:30-08:50 Yale Passamanack (Postdoc, Univ. Hawaii) “Early photoreceptor development in brachiopods, and the evolution of morphological complexity”

I’ve been here before

  08:50-09:10 Neva .P. Meyer (Postdoc, Univ. Hawaii) “Central nervous system development in the annelid Capitella teleta”

Simple nervous system, lovely images of serotonin staining. They’ve got a small brain produced by cells dividing on surface, then migrating inward by bottle cell formation. Anterior epithelium becomes multiple-layered; internalized cells do not divide further. Pro neural genes expressed — similar to insects. Knockdown of achaete-scute homolog causes loss of synaptotagmin, blocks brain formation.  Neurogenesis in Capitella resembles myriapod dev.

I think I’m going to have to talk about Capitella in my fall neuro course.

  09:10-09:30 Andy Ransick (Faculty, Cal Tech) “Developmental mechanisms accompanying the evolution of echinoid larval mesoderm”

Echinoids have a unique pattern of early divisions. What follows is an Eric Davidson style analysis of molecular circuitry. There is a kind of double negative logic to activation of this module, with parts of the network dedicated to stabilizing output.

Micromeres are an evolutionary novelty that creates a new signalling center. Ransack discusses the regulatory module that is active here.

Incoming! Here’s another dump of my notes from yesterday afternoon. I’ll be hitting you with more later today.

Disease is the pretext here, but it’s really all about development.

15:30-17:00 Session 4: Development and Disease (Chair: Jack Somponpun [Univ. Hawaii]; co-Chair: Jacqueline Ho [UPMC])

15:30-16:00 Jacqueline Ho (Children’s Hospital of Pittsburgh UPMC) “microRNAs in kidney development and disease”

Congenital anomalies are most common cause of renal failure in children.  Kidneys form from metanephric mesenchyme by induction from branching tubule – lots of interactions and opportunities to go awry. She’s looking at effects of miRNA. Loss of mRNAs in podocytes of glomerulus using transgenic mice leads to fetal death — they are necessary for formation of filtration barrier. Loss of miRNAs in nephron progenitors leads to depletion of population. Imbalance between selection for differentiation vs. Self-renewal?

There is no difference in proliferation. There is an increase in apoptosis.

Next problem is sorting out which of the many miRNAs deleted are important. Using bioinformatics tools to predict miRNA target interactions. Found candidate gene target, Bim, and identified miRNAs that might be modulating it’s expression.

Balance between survival (Bcl2) and apoptosis (Bim) that is tipped by miRNAs.

  
  16:00-16:20 Jack Somponpun (Faculty, Univ. Hawaii) “Reduced embryonic Six2 expression compromises nephron development and leads to osmoregulatory defect associated with post-natal fluid and electrolyte handling”

Variation in nephron number in population: as few as 200000′ as many as 2.5 million, average of about a million. Is this normal diversity or is it a consequence or cause of health problems? Kidneys are most important organ for regulation if bulood pressure. What is the significance of low nephron number?

Brachyrrhine mutant mice — greatly reduced kidney size, shows haploinsufficiency. Six2 is expressed strongly in embryonic kidney; thought to play a role in maintaining size of progenitors populations and preventing premature differentiation. Looked at Br mouse and also used siRNA to reduce six2 in cell culture system.

Br mutants have reduced number of nephron rudiments and reduced Six2 expression.

Inhibition of Six2 in culture also leads to reduced number of nephron rudiments. Also up regulates WT1, reduces Pax2, Cited1.

Reduced kidneys in Br mice have physiological effects. Can’t cope as all with increased salt in diets — hypeerosmolalitu, hypernatremia, polydipsia, with urine-concentrating defect, comparable to chronic renal failure.

  16:20-16:40 Grant Miura (Postdoc, UC San Diego) “The T-Box Transcription Factor Tbx20 is required for the maintenance of proper cardiac chamber size”

Early development of heart: mustw balance size of ventricle vs. Atrium. Laf mutant reduces atrium size. Tinkeering with BMP pathway affects relative size of atrium/ventricle. BMP Important; what are other signals, and what are downstream targets? Screened small molecules known to cause cardiovascular defects. 

Searched for genes with SMAD binding sites, which led to Tbx20 gene. Tanscription factor with conserved expression in flies and vertebrates. Tbx20 morpholinos caused serious cardiac edema, otherwise normal. Decreased both atrial and ventricular size, but early specification was normal. Doesn’t look like laf at all. Regulates proliferation or maintenance?

  16:40-17:00 Denise Al Alam (Postdoc, Saban Research Institute) “FGFR2b signaling is required for the formation of lipofibroblasts in the developing mouse lung”

Bronchopulmonary dysplasia — preemies treated with oxygen end up with surfactant deficiency, decrease of lipofibroplasts and FGF10. lipofibroblasts required for surfactant synthesis. FGF10 through FGFR2b required for differentiation. Used Dom-neg receptor to knock down FGFR2b.  Reduces lung differentiation.

Well, a whole room full of them, actually, but also the proud nerd and meeting crasher Christie Wilcox, who, I now learn, has a darned good set of pipes.

This session is all about pattern formation, focusing on those earliest, simplest decisions. How doe a mass of identical cells distinguish themselves inti regions with different patterns of gene expression. You might recall that this is the question that so baffles the creationist Paul Nelson. Nobody is going to give a moment’s consideration to his concerns, because they aren’t at all interesting.

10:30-12:00 Session 2: Pattern Formation (Chair: Vernadeth Alarcon [Univ. Hawaii])

10:30-11:00 Vernadeth Alarcon (Univ. Hawaii) “Cell polarity and differentiation in the early mouse embryo”

Studying the preimplantation mouse embryo, and the cell fate decision of committing to extra embryonic tissues vs embryo proper: trophectoderm(te) vs inner cell mass (icm). How does the embryo make TE? TE cells are polarized- they have apical and basal sides; does this play a role in differentiation? Found homologs to nematode partitioning defective genes (pard6b) that may be part of the mechanism. Knockdowns of pard6b leads to failure of blastocyst formation. It is essential for epithelialization of cells, which is a consequence of polarization. Knockdown also leads to reduction of trophoblast derivatives, while ICM derivatives are upregulated. 

Another gene involved in trophoblast differentiation is tead4. Tead4 knockdown also leads to failure of blastocyst formation.tead4 doesn’t seem to effect epithelialization, though — cells stilm make tight junctions independently of trophoblast differentiation, suggesting that these are separate pathways regulated by pard6b.

  11:00-11:30 Magdalena Zernicka-Goetz (Univ. of Cambridge, UK) “Mechanism behind formation of distinct cell lineages in the mouse embryo”

Let’s add more decisions: ICM vs TE, then Epi vs PE, then AP axis. Multiple competing models for first decision: early asymmetry, which was shown to be problematic because this cells are not committed. Another is the polarization model, complicated by the inside-outside model. Speaker says she’s going to propose all three models are correct tomvarying degrees. Aargh, biology is complicated.

Polarity develops at 8 cell stage, down regulation of pars influences these decisions. Also forms outside an inside cells with division at 8 cell stages. Some outside cells divide to make 2 outside cells, others to make one out and  one in..what causes this difference? High cdx2 causes conservyative divisions, low yields differenitiative, so there is a molecular bias. Notnrandom, but not tightly regulated either. Cdx2 also localizes apically as cells polarize. There is a positive feedback loop between polarity and cdx2, maintaining inside-outside polarity.

Second decision of primitive endoderm vs epiblast: random or pre-specified/biased? Used 4D tracking of cells and fate decisions, developing pedigrees of cell fates. First wave of divisions is biased to produce Epi, subsequent waves biased to produce PE — so not random. Salt and pepper pattern is an accident of poorly defined position of blastocyst cavitation.

25% of ICM cells undergo apoptosis! What an inefficient business development is.

  11:30-11:50 Saori Haigo (Graduate student, UC Berkeley) “Global tissue rotation: a novel polarized morphogenetic movement that controls tissue elongation and egg shape in Drosophila”

Flies! New question: how do flies make an ellipsoid egg? It’s another issue of developing asymmetries.

In this case they’re looking at follicle cell epithelium that surrounds the maturing egg. Mosaic mutants in follicle cells can produce round rather than ellipsoid eggs. What are the follicle cell behaviors that promote elongation?

Follicle cells undergo constant, sheet like migration orthogonal to elongation — cool movies of rotating follicle cell layer, at rate of 0.5µm/min. Waaa, I want a confocal microscope of my own!

Round egg mutants suppress rotation. How does rotation cause elongation, though?

Collagen IV forms a polarized fibrillar matrix during rotation. Basically it’s laying down circumferential fibers- a “molecular corset”. The collagen is not oriented/polarized in round egg mutants.

  11:50-12:10 Ankita Das (Graduate student, Univ. of Southern California) “A Bmp-Id2a-Twist1-Fli1a network specifies ectomesenchyme from neural crest”

Ectomesenchyme is important in formation of vertebrate head–they are derived from neural crest, which uniquely forms ectomesenchyme in head but not trunk. How does zebrafish head skeleton (branchial arches) form? What is the signal to make ectomesenchyme?

Markers: sox10, dlx2a. They’re looking for the regulators of these key genes. Some nc cells start expressing dlx2a as soon as they start migrating, suggesting mesoderm may not be source of signal. There is a change in BMP expression as they form ectomesenchyme — down regulation of BMP may be a trigger. Misexpresion of BMP4 causes defects in EM specification. Hi BMP activates sox10, leads to non-EM. As th cells migrate away, declining BMP permits dlx2a expression and EM fate.

Losing Twist1 has similar effect; Twist1 may also promote EM formation. What suppresses Twist1? Another gene, id2a, that is target of BMP4 and in turn supresses dlx2a. Misexpresion  of id2a also produces errors in EM development. They’ve put together a nice picture of the gene circuitry behind specification of ectomesenchyme.

Here we go, I’m attending the West Coast Regional Meeting of the Society for Developmental Biology, and I’ll be intermittently dumping my notes onto the web, so that’s what you’ll be getting today — my sometimes cryptic impressions of a series of developmental biology talks.

This is the early morning session. It’s late in the day for this Minnesotan, though…but beware, that just means I may start flagging this afternoon.

08:30-10:00 Session 1: Stem Cells in Development and Regeneration (Chair: Monika Ward [Univ. Hawaii])

Hey, speakers get lei’ed at the start of their talk! I guess I really am in Hawaii.

  08:30-09:00 Venugopala Reddy Gonehal (UC Riverside) “Systems level dynamics of cell interactions in plant stem cell niches: Live imaging and microgenomics”

Looking at shoot apical meristems and plant stem cells in Arabidopsis. Very cool time-lapse of plant meristems. Cell cycle length of 70-80 hours! Ouch. But still…lovely fluorescent markers of various stem cell niches, and they can examin stecell dynamics in mutants. They are using experimental data as input to mathematical models that they test in simulations. Looked at two mutants: clavata3, a secreted peptide, that leads to over-expansion of stem cells, and wuschel, a homeodomain containing trancription factor, that leads to an absence of stem cells. Increasing wuschel levels leads to expansion of the stem cell domain; using chip assays, they have worked out the response genes in this pathway…and they’re more transcription factors. 

One weird surprise: a gradient of a diffusible transcription factor that moves through plasmdesmata to induce up regulation. I guess it’s a plant thing. I spend too much time in just animal models.

Reddy’s models (shown in some very pretty simulations) can account for the generation of the patterns of gene activity in the meristem, and also accurately respond to mutations in the same way that the live tissue does.

  09:00-09:20 Kate Lynn Jaremko (Graduate student, Univ. Hawaii) “Regulation of developmental competence and commitment during endoderm and neuroectoderm differentiation in human embryonic stem cells”

Looking for ways to induce ectoderm and endoderm differentiation in hESCs, using activin signalling.  She’s giving a nice clear introduction to the concepts of competency and specificity in development. Low levels of activin signaling are required to maintain pluripotency; inhibiting activin promotes  ectoderm differentiation. experiments involve specifically timed exposures to activin or activin inhibitors , followed by examination for markers for differentiation. 

This is straightforward modern developmental biology: tinker with th molecular inputs, look at the molecular outputs, and figure out effective ways to nudge the development of a cell in a direction you desire.

  09:20-09:40 Jonathan M. Riel (Graduate student, Univ. Hawaii) “Functional deficiency of the mouse Y gene Sly leads to sperm DNA damage and abnormal chromatin packaging”

mouse has 50 copies of Rbmyf1a1 on the Y chromosome. They’re  working with a strain of mice with reduced fertility, using ICSI to get progeny. They noticed a significant difference in fertility with sperm from epididymis vs. Testis in mice with deficiencies in NPYq — traced to problems in protamine processing, suggesting that there is an NPYq gene involved in packaging and maintaining sperm DNA. Loss of the sly gene leads to abnormal sperm heads, and this work tests whether it is specifically an sly deficiency that leads to poor sperm maintenance in their mice. Loss of sly leads to a loss of membrane integrity and slightly to severely decondensed DNA condensation.

Conclusion: sly is involved in DNA packaging in spermatogenesis. Ok, I’ll believe him.

  09:40-10:00 Catherine D. McCusker (Postdoc, UC Irvine) “Insights into the establishment of positional information in the limb blastema”

Limb regeneration requires interaction with nerves — they can even induce blastemas by routing a nerve to a wound site, although it won’t regenerate into a new limb. That also requires positional information in the epidermis. The standard model invokes gradual specification by a progress zone in th egrowing limb bud. An alternative is that the full range of proximodistal morphologies are pre specified in the early limb bud.  Pre specification supported by transplant experiments that seemed to show that zones of the blastema had limited developmental potential. Distal blastemas should only be able to make distal tissues, however, new experiments with better markers show that transplanted blastemas can regenerate more proximal tissues. Thes new results suggest that the blastema is NOT pre-specified.

The basal region of the blastema is committed, and transplants will induce duplicated proximal structures.  Apical region of the early blastema does the same thing.  The new model is one of progressive specification of basal cells while apical cells are more plastic — a hybrid of the progress zone model and the pre specification model.

Talk also had pretty picture of lovely stained regenerating limbs. I’m a sucker for nice morphology.

Once upon a time, there was a man who thought rather highly of humanity’s potential. Sure, there were things humans did that were awful — they could be violent, and careless, and short-sighted — but they also did amazing things like science and art that other species didn’t. Overall, he thought that calling someone “human” was a high compliment. And this idea colored his thinking in such a way that it began to shape his expectations of people; maybe we should expect human beings to do more than eat and excrete and reproduce, and maybe we should recognize that the word “human” meant an awful lot more than just a certain flavor of meat or the species of your parents.

He also noticed that every single human being he ever met, without exception, was more than a perambulating set of chromosomes. Some were good at math and others liked to dance and others were kind and yet others liked to argue, and these were the virtues that made them good and interesting, and made them…human, in this best sense of the word. So when he praised being human, it wasn’t for the accident of their birth, it was for the qualities that made being human meaningful.

Unfortunately, not all humans liked having the fact that words carry greater connotations than the most narrow, most literal, most concise, dictionary-style definitions, despite the obvious fact that they all do. They got quite irate.

“I am a human because I am not a squirrel, or a hyena, or a fish, or broccoli,” some said, “and I resent the fact that you think there’s more to me than being a not-squirrel!”

“You expect me to be good at math to qualify as human?” complained some of the slower, less alert people, who failed to notice that the man had made no such specific requirements.

“The only thing that all humans have in common is that they were born to other humans, and can only reproduce with humans,” said other complainers, “therefore, that is all that ‘human’ can imply or mean. How dare you taint my pure and perfect language with complications and nuances and expectations!” 

And the man listened to their arguments for a while, and argued back for a while, and then he came upon a simple solution. He told the not-squirrels and identity-by-rutters and functional illiterates and simple-minded machine-coders to fuck off, and it was good.

“Ad hominem!” they squeaked.

“Who cares what barely human people think, anyway,” he shrugged.

We Gnu Atheists, and atheists of all kinds, are often accused of following “just another religion.”  I’m not particularly fond of the usual riposte — something along the lines of sarcastically pointing out that atheism is a religion like not collecting stamps is a hobby — because I think we sell ourselves short when we pretend atheism is an absence of values rather than a positive and powerful collection of strong modern beliefs, but also because there are distinct differences in the way atheists should think, relative to theists. I say “should” because, often, where I see the starkest contrast is in atheist apologists for religion, who sometimes seem to be unbelievers still trapped in old modes of thought.

Jaques Berlinerbau is one such infidel locked in a medieval mind; he links approvingly to a long-winded, plodding essay by R. Joseph Hoffmann, who reminds me of nothing so much as a pompous clergyman, who has little too say but will puff it up into a good solid tendentious drone ands mercilessly slaughter all of his critics with ennui. They have another old criticism of the Gnu Atheists: we have a shocking deficiency of martyrs.

Say what? We’re supposed to build our movement on corded stacks of dead atheists, preferably ones murdered by torture, or Hoffmann and Berlinerbau will not take us seriously? I can’t think of a better example of the blinkered brains of our critics. Religion, especially Catholicism, loves to dwell on torment and death and finds validation, even, in the agonies of the faithful; why, God must be really, really important if his followers will throw their lives away for him. Hoffmann seems to be impressed with this line of thought, and tries to argue that atheists should grant more credit to the distinguished line of martyrs, often believers, who died to advance the cause of freethought. He thinks we ought to be more appreciative of Bruno and Servetus and Hus and Aikenhead for their deaths in the name of a cause.

Personally, I recoil in disgust at the thought. We should celebrate the lives of good people, not their deaths. Their deaths do not contribute to a cause, they only stand as testimonials to the bloody oppressive nature of our enemies; all would have served humanity better had they lived. We should no more find vindication in the execution of heretics than doctors would revel in the glory of millions of miserable deaths to typhoid and cholera and smallpox and childbed fever — we should want to simply end these horrors. A trail of tears is not a victory parade.

Atheists should not want martyrs, and neither should we desire the deaths of our opponents. Death is an end and a loss and not any kind of virtue, and that Berlinerbau and Hoffmann have these antique fantasies of good godless corpses piling up to lend gravitas to the movement, or that the vocal Gnu Atheists even imagine such a story would be desirable, says quite a bit about their inability to think beyond their obedience to a theological mindset. While they reject the notion of a god, they continue to pay homage at the altar of religious morality.

It’s god to see I’m not alone in rejecting their entire premise. Both  Jerry Coyne and Ophelia Benson express similar sentiments. There really is a coherent and consistent Gnu Atheist consensus that is very different from the horrid old modes of religious thought, and it takes an unimaginative and narrow mind to think otherwise.

I have learned that today is Christopher Hitchens’ birthday. I hope he gets many more.

What is it with all these New Atheist birthdays in the springtime, though?

I have a request to all of you. Some of you hate me, so you’d enjoy this, but it’s more important that those of you who have a mild and distant affection for me take a stand, too. If, sometime in the future, when the billions of dollars role in, if you learn that I’m flying in children for sex, I don’t want you to defend me. Don’t use friendship as an excuse, just come out loud and clear and denounce my behavior, with no qualifiers. Please. There aren’t any justifications or rationalizations possible.

I am not planning to turn into a leering old degenerate, but you never know…I could suffer traumatic brain damage that radically alters my behavior, turning me into either a lecher or a Christian. If such a horrific event occurs, consider me dead and start abusing the bankrupt personality residing in my corpus, OK?

Ditto if I start robbing banks, beating up little old ladies for their social security checks, praising the Templeton Foundation, or become a Mormon. That stuff is just wrong.