D V High [Dorsal] Low [Dorsal] No Dorsal Graded Dorsal Concentration Created by Mother Hierarchy of Gene Action in D/V Patterning Mesoderm Genes Neuroectoderm Genes Non-neural Genes D/V GenesBasic Tissue Types Controlled by Embryo

= Mesoderm= Non-Neural Ectoderm= Neuroectoderm Epidermal Genes Dpp Neuronal Genes AS-C RhoVentral Epidermal Genes Neural Genes Twist Mesodermal Genes Snail Neural Genes Brk, Sog Dorsal Genes

Dorsal meso neuro epi snail dpp “sog” sog dpp

dpp versus sog Expression sog dpp

DA Dorsal Region Cell Inside Outside OnOff Repressor From Mother N Nucleus Regulatory Region Coding Region Nucleus Dorsal or Lateral Region Cell Inside Outside Dpp Receptor Sog Signal Relay OnOff Non-neural genes (e.g. dpp) OnOff Neural genes (e.g. AS-C) dpp mRNA No Dorsal Dpp Protein Dpp versus Sog Function

Mesodermal Genes Neuronal Genes = Mesoderm= Non-Neural Ectoderm= Neuroectoderm Dpp Sog dpp- versus sog- Mutants X Neuronal Genes Epidermal Genes

Mesodermal Genes = Mesoderm= Non-Neural Ectoderm= Neuroectoderm dpp- Mutant Neuronal Genes Sog

dpp- Mutant

Mesodermal Genes Neuronal Genes = Mesoderm= Non-Neural Ectoderm= Neuroectoderm Dpp Sog sog- Mutant X Neuronal Genes Epidermal Genes

Mesodermal Genes = Mesoderm= Non-Neural Ectoderm= Neuroectoderm Dpp Neuronal Genes Epidermal Genes sog- Mutant

The Default State of Ectoderm is Neural

Sog diffuses and patterns the dorsal region The Players Dpp: A signal that promotes dorsal fates Sog: A secreted inhibitor of Dpp Tolloid = Tld: A protease that cleaves and destroys Sog

Dorsal Ventral Tld Low BMP Hi BMP BMP Sog Non-neural Ectoderm Amnioserosa Sog diffuses and patterns the dorsal region

A Sog protein gradient forms dorsally Epi Neuro Meso A P V D sog RNA/ Sog Protein

Sog protein/dpp RNA Tld limits Sog accumulation dorsally WTDf(tld)

Sog Creates a BMP activity gradient dorsally SogDpp VD [Sog] 1) A dorsal Sog gradient is created by a ventral source and dorsal sinks for Sog. Relative BMPActivity 2) A reciprocal BMP activity gradient forms. 3) Dorsal region is subdivided into two domains. Non-neural Ectoderm A.S. race

Dpp diffuses and patterns the ventral region - High levels of Dpp signaling in dorsal cells represses all neural genes - Low levels of Dpp diffuse ventrally - Some neural genes are more sensitive than others to Dpp repression (e.g., ind is more sensitive than msh) - Differential sensitivity to Dpp repression creates pattern in the neural region (the least sensitive gene, msh, can be expressed closest to Dpp source)

= Mesoderm= Non-Neural Ectoderm= Neuroectoderm High Low None [Dorsal] High Low None Dpp Non-neural genes Neural genes Dorsal Subdivision of the Neuroectoderm Neuronal genes Msh Ind Vnd

Drosophila Neuroectoderm Mouse Neural Tube Sonic Hh BMPs MsxNkx2.2Gsh Dorsal Dpp ind msh vnd dpp Patterning the Neuroectoderm in Flies and Mice

ind vnd msh D V Ventral Dominant Repression

vnd Dpp signaling represses ind more effectively than msh mshind Dpp X ind

ECT NE MES BrkDpp st2-brk Dpp signaling represses ind more effectively than msh

Sog Dpp VD [Sog] [Dpp] Relative BMPActivity 2) A BMP repression gradient forms within the neuroectoderm -> Three rows of neuroblasts. mshindvnd Neuroectoderm 1) A Sog gradient creates an inverse BMP activation gradient dorsally -> Non-neural Ectoderm vs Amnioserosa. Non-neural Ectoderm A.S. race Reciprocal Patterning of the Ectoderm by Sog and Dpp

BMP signaling in the neuroectoderm of flies and vertebrates