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.Â
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.
Â Â 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 Â 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.
Â Â 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.
Â Â 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 Â of id2a also produces errors in EM development. They’ve put together a nice picture of the gene circuitry behind specification of ectomesenchyme.