A few notes: -Lectures are posted on Blackboard under “Course Materials” tab -Non-textbook readings are posted under the “Reserves” tab -Attendance is not mandatory but highly recommended! Localized determinants and asymmetric cell divisions establish the body plan of the early embryo Body axes: 1) Animal-vegetal 2) Dorsal-ventral 3) Anterior-posterior 4) Left-right Gastrulation and neurulation in the frog embryo Development of the nervous system from the gastrula Formation of the notochord and neural tube BMPs, Wnt in neural plate ectoderm Shh secreted from notochord & floor plate Neural tube closure triggers neural crest delamination *No neural induction w/o competence conferred by mesoderm *Neural induction occurs because of signaling from mesoderm What is an “organizer”? Spemann and Mangold implicate the dorsal lip of the blastopore in neural induction Neural fate is suppressed by contact-mediated inhibition in ectoderm BMP signaling (TGF-beta superfamily) Nature Reviews Rheumatology 6, 518-527 (September 2010) TGF-beta superfamily of signal transduction Blocking TGF-beta like signaling causes animal cap tissue to become neural Secreted ligand BMP4 suppresses neural fate in ectoderm no Ca2+ Mesoderm induction in frog embryos: A + V = M (or Ec + En = M) Neural induction Dorsalizing Xenopus embryo: activates Noggin to suppress BMP signaling = neural fate Noggin, Chordin: Neural inducers UV blocks cortical rotation; Li+ blocks PI signaling/ increases chordin via gsc Sperm entry point induces cortical rotation to induce dorsal organizer (vegetal cx + animal cytoplasm) … and: animal cx + vegetal cytoplasm = ventral Chordin: in the right place at the right time… Chordin injection Secondary axis wt Noggin -/- Noggin -/-; Chordin -/- Mechanics of the organizer and gastrulation in frog Cerberus, Chordin, Noggin, Follistatin (meso/endo) vs. BMPR & BMP4 (ectodermal) Fgfr & Fgf8 (neural) The epidermal-neural switch: BMP off + FGF on Zic1/Zic3 required for neural plate In Drosophila, ventral nerve cord derives from condensed neurons & glia In flies, dpp= BMP (blocks neural), & sog= noggin/chordin (promotes neural) Position of cells determines level of exposure to morphogen what the cell will be when it grows up Morphogens drive differential gene expression Cells acquire positional information in the limb bud Fgf8 = blue (AER) Shh = red (polarizing region) Yellow = proliferating progenitors Shh in the polarizing region Grafting of ectopic polarizing region causes digit duplication Restriction of Gene Expression Transcription factor “zip code” sets the map of positions where motor neurons or interneuron subtypes will differentiate Opposing morphogen gradients pattern the D-V axis of the spinal cord Dorsal neural tube: BMP4 Ventral neural tube & notochord: Shh Motor neuron differentiation depends on Shh and the notochord Levels of the diffusible morphogen Shh pattern the neural tube: low = dorsal (Pax 7) medium = middle (Olig2) high = ventral (Nkx2.2) Neural tube dissections: Increasing BMP4 levels leads to dorsal fate specification, even in the presence of Shh (Liem et al, 1995) Ectoderm = source of BMP4; turns on TFs Msx1/2, HNK1, slug Dorsal ectoderm, then dorsal neural tube cells express BMPs; ventral notochord then ventral floorplate expresses Shh