Neurulation & Organogenesis

Neurulation

• Neural cells originate from the neurectoderm

• Clusters of proneural cells are specified by the proneural genes

• Single neuroblasts are specified within the proneural cluster via lateral inhibition

• Proneural and neurogenic genes, respectively, regulate these specification events

Neurogenesis

Proneural & Neurogenic Genes

• Proneural: Achaete-Scute complex of genes (AS-C)– Achaete (ac), scute (sc), lethal of scute (lsc), asense (as)

• Neurogenic: Notch-Delta pathway– Notch (N), Delta (Dl), Enhancer of split (E(spl)), Hairless

(H), Suppressor of Hairless (Su(H)), brainiac (brn), mastermind (mam), neurlalized (neu), kuzbanian (kuz), big brain (bib)

Acheate Expressionen = purple acheate = black stain

Regulation of Proneural Genes

• hairy (h), gooseberry (gb), Extramacrochaete (emc) – Emc & h are inhibitory bHLH txn factors

– Gb has a homeobox

• ventral nervous system defective (vnd), engrailed (en), wingless (wg), iroquois (iro)

Neurogenic Genes• Juxtacrine signaling

molecules

• Delta (Dl) - ligand

• Notch (N) – receptor

• kuzbanian (kuz) – protease kuz

Su(H)E(spl)

Delta-Notch Signaling

by kuz

Lateral Inhibition Summary• Delta and Notch are expressed in every cell in the proneural

cluster• Dl is usually slightly more highly expressed than N

• Dl activates N• N activates Su(H)• Su(H) displaces H and activates E(spl)• E(spl) inhibits AS-C genes & indirectly, Dl• Without AS-C gene products, neural differentiation is

blocked• AS-C normally activates Dl and other proneural genes

Drosophila Neurogenesis & Vertebrate Neurogenesis Occur Via Homologous Pathways

Mash – mouse acheate-scute homologueDll-1 – delta-like 1

Delta-Notch Signaling in Vertebrates

Drosophila Peripheral Nervous System• proneural clusters form in imaginal discs

• proneural clusters differentiate into SOPs and ultimately into sensory bristles

Differentiation of Sensory Bristles

numb & Notch mutations

SMC (sensory mother cells) also called SOP (sensory organ precursor)

no SMC

OrganogenesisImaginal Disc

Imaginal Discs

Initial Specification of Imaginal Discs

Intersection of wg stripes with Dpp expressing cells specifies discs

Leg Disc Primordia

Wing/HaltereDisc Primordia

Patterning of Wing Discs

Anterior-Posterior specification established by en, & hh with Dpp

at the border

Dorsal-Ventral Polarity in Wing Disc

Apterous protein (green) dorsal wingVestigial protein (red) ventral wing

Wing Disc

Patterning of Wing Discs

dorsal-ventral patterning is established by apterous & vestigial

expression with wg establishing the border

Patterning of Wing DiscsVestigial (green), apterous (red), wingless (purple), cubitus

interuptus (blue)

Patterning of Leg Discs

Eversion of Leg Imaginal Disc

Proximal-distal Axis in Leg Disc

Expression of txn factors in regions of leg disc specifies proximal-distal polarity distalless (dll)(red), dachshund (dac) (green), homothorax (htx) (purple)

Eye Disc Specification

Twin of eyeless(Pax6)

Eyeless (Pax6)

Eyes absent(eya1, 2, 3)

Sine oculus(Six3)

dachshund

Ectopic Expression of ey

Patterning of the Eye Disc

Differentiation in the Eye Disc

AP

Morphogenic Furrow

Progress of Morphogenetic Furrow & Cell Specification in Its Wake

Rhabdomere Specification

Drosophila Compound Eye

Ommatidium 20+ cells;

8 photoreceptors12 accessory cells

800 Ommatidia

Drosophila ommatidium

Go See an Ommatidium @

http://sdb.bio.purdue.edu/fly/virtomm.mov

Analysis of R7 Differentiation through Genetic Mosaics

sev only needed in R7 for R7 differentiationsev functions cell autonomously