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	Signaling cues for different identities Ventral Dorsal Rostro-caudal
Show me what the notocord does	Spinal cord & Neural crest
Ectoderm neurodetermination for spinal cord

Spinal Cord

• laterally "symetrical" antero-dorsally and rostro-caudally different.
• contains: motor neurons, interneurons, glia.

Neural Crest

• not intrinsic part of SC development but is neural and in intimate contact with early SC.
• migrates to different embryonic regions
• migration regulated by substrate (adhesion) mediated cues (pathways).
• neurons generate processes tht contact effector organs and SC neurons.

How do you generate axes?

• signaling cues for different identies
• Ventral-Dorsal
• Rostro-Caudal

Ventral

• Experimental manipulation of interactions.
• Initial experiments looked at how isolated tissues may influence the development of the spinal cord.
• Repositionining of specific tissues both in vivo and in vitro
• specific markers of or alteration of differentiation.

Results

• notocord induced spinal tube formation.
• notocord induced floorplate formation.
• floorplate induced ventral spinal cord [motorneurons]
• posterior ectoderm induced dorsal spinal cord [interneurons]

Dorsal

What other signals have been evolutionarily conserved and reused?

• frog growth factor controls patterning in embryonic mesoderm (TGFb)
• flies related protein determines dorsoventral
• homology search of vertebrate library identified protein of same family.
• dorsalin-1 (dsl-1)
  • Basler et al., Cell 73, p687, (1993)

Dorsalin-1

• Naming comes from the obvious reason that it promotes the differentiation of neural crest cells.
• Also signal for dorsal signal of neural tube.
• Inhibits the differentiation of motoneurons.
• Implication is that dsl-1 and shh act antagonistically, or competitively to establish d-v axis of neural tube.

Rostro-Caudal

What about the third pattern axis?

• Brain rostro-caudal axis is generated by differential expression of Hox genes.
• Transcriptional activators.
• corresponding to genetic order on chromosome.
  • Wilkinson et al., Nature, 341, p405 (1989).
• SC Organization
• Hox Gene Expression-SC
• Hox related family of proteins (LIM) contain slightly different DNA-binding domain.
• LIM genes originally isolated from C. Elegans ( a worm).
• LIM genes differentially expressed along rostro-caudal axis.
  • Tsuchida, Cell 79, p957, (1994).

LIM Gene Expression

• Differential expression means a different member of this protein family is expressed at different segmental levels.
• Just as Hox for the brain.

Chicken LIM genes

• Islet-1, Islet-2, Lim-1, Lim-3
  • Lumsden, Current Biology 5, p491, (1995).

LIM Expression & Motoneuron Populations

MMC- Medial Motor Column (trunk) MMCm (medial) axial near vertebra	MMCl (lateral) ventral body wall LMC Lateral Motor Column (limbs)	LMCl (dorsal)	CT- Column of Terni (visceral)

LMCm (ventral)