University:
Amherst College
Course:
BIOL 220 | Developmental Biology
Academic year:

2023
Views:

234

Pages:

22
Author:

Brennen Smith

The Organizer Back to the Organizer: “Primary” Induction What Does Spemann’s Organizer Do? • Mesoderm that dorsalizes the embryo: – Becomes dorsal mesoderm (prechordal plate, chordamesoderm) – Induces nearby mesoderm to form lateral mesoderm (rather than ventral) – Induces ectoderm into neural ectoderm – Initiates gastrulation – Induces neural plate to become neural tube How to Find the Real Organizer Molecules? • What are the molecules responsible for these inductions/organizations? – Some biochemical experiments (1930s -1940s) seemed to belittle the all-powerful organizer • • • • Dead organizer tissue pH or ionic composition Turpentine, alcohol But only live tissue of organizer could do it – Suggested that responding tissue (not inducer) had specificity but something unleashed it • Molecular approaches to find the real signals There Are Many Isolation of First Soluble Organizer Molecule: Noggin – Inhibits ventralization • Extract mRNAs – copy into DNA and amplify – Inject pools into ventralized embryos (UV) • Look for dorsal tissue formation Increasing noggin mRNA • Li+ treated embryos (dorsalized) Where is Noggin mRNA Localized? gastrula dorsal marginal zone dorsal blastopore lip notochord What Does Noggin Do? • Secreted protein – Induces dorsal ectoderm -> neural tissue – Dorsalizes mesoderm • Acts by binding other secreted proteins – BMP4 and BMP2 – Prevent receptor interaction – So dorsalization by inhibiting other signals? New Concept: Epidermal Induction • Is neural fate the “default” ectoderm fate? – Epidermal fate the “induced” fate? • Cell dissociation studies • Dissociated animal cap cells --> neural tissue! • Suggests neural fate = default fate • The organizer prevents induction in preneural ectoderm Then What Is the Inducing Molecule for Ventral Ectoderm and Mesoderm? • BMP-4 is present in the marginal zone except in dorsal-most region • Injection into embryos has ventralizing effect – all mesoderm develops as ventrolateral mesoderm with no gastrulation) Other Diffusible Factors are Also BMP Antagonists • Inhibition by chordin – mRNAs in dorsalized not ventralized embryos – Injection to produce 2o axis – Binds to bmp2, bmp4 • Inhibition by Xnr-3 (nodal) same • Inhibition by follistatin – Inhibits activin related proteins • All prevent BMP binding to receptors BMP Antagonism Model of Organizer Action How Are Different Mesodermal Regions Specified? • BMP-4 activates genes in a concentrationdependent fashion • Rough model – – – – [High] -> blood [Med] -> kidney [Low] -> muscle [None] -> notochord The Head Region • The most anterior region is induced not by notochord but by endoderm and head mesoderm • Signals here are BMP and Wnt8 (Xwnt8) • What antagonizes Wnt8 in the head region? The Anterior Endomesoderm Two Types of Inhibitors Dorsal Posterior BMP inhibitors Dorsal Anterior Wnt inhibitors What are the Wnt Inhibitors? • Cerberus – Expressed in endomesodermal cells of early blastopore lip – Induces ectopic head structures if injected into ventral vegetal region of blastula – Promotes formation of anterior-most ectoderm • cement gland • eyes • olfactory placodes – Can bind to BMPs and Xwnt8 What are the Wnt Inhibitors? • Frzb and Dickkopf – Soluble proteins that also interact with Wnt proteins • Expressed in endomesoderm beneath the future head • If overexpressed -> “big head” embryos – Wnt signaling is prevented everywhere and therefore excessive head induction is allowed to occur An Ultimate Frzb Game Extra Frzb blocks Wnt signal Control Injection of Frzb mRNA Wnt Antagonism Model of Head Organizer Action Model of Mesoderm Induction: Gradients of BMP4 and Xwnt8 Set Up by Xnr Gradient V + b-cat give nodal gradient Organizer Paracrine Factors Antagonists • Battles in extracellular space! – Head + brain: no BMP or Wnt – Trunk: Wnt but not BMP – Epidermis: Wnt + BMP • Graded series of inhibitors these tissues secrete these factors

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