Neurons are diversified by the intersection of three patterning mechanisms:
1, Spatial compartmentalization of the neuroepithelium into at least eight spatial regions by transcription factors (TFs) and signaling molecules.
2, Temporal sequence equential expression of at least 11 temporal TFs (tTFs) in neuroblasts (been detailly told in the previous passage).
3, Notch signaling between sister neurons.
1, Spatial compartmentalization
3 regions: Outer proliferation centre (OPC) neuroepithelial crescent can be subdivided along the dorsal–ventral axis by the mutually exclusive expression of three homeodomain-containing transcription factors: Vsx1 is expressed in the central OPC (cOPC), Rx in the dorsal and ventral posterior arms of the crescent (pOPC), and Optix in the two intervening ‘main arms’ (mOPC).
2 regions: The OPC can be further subdivided into dorsal (D) and ventral (V) halves.
3 X 2 = 6 compartments + plus the pOPC compartment can be further subdivided by the expression of the wingless and dpp signalling genes. Cells in the wingless domain behave in a very distinct manner from the rest of the OPC. = 8 regions in total.
Neuroblasts produce the same uni-columnar neuronal type globally as well as smaller numbers of multi-columnar cell types regionally.
Regional differences in the OPC confer further spatial identities to neuroblasts with the same temporal identity, and lead to specific differences in the lineages produced in the compartments along the dorsal–ventral axis of the medulla. These differences produce smaller numbers of multi-columnar neurons whose stoichiometry is much lower than 1:1. This combination of regional and global neuronal specification in the medulla presents a powerful mechanism to produce the proper diversity and stoichiometry of neuronal types and generate the retinotopic map.
Shows the nonreduntant regional specifc gene expression.
3, Notch On/Off
Apterous (Ap) is known to mark about half of the 70 medulla neuron types. In the larval medulla, Ap is expressed in a salt-and-pepper manner (sparse) in subsets of neurons born from all temporal stages. In the progeny from Hth+ neuroblasts, all neurons seem to maintain Hth (relatively irregular), with a subset also expressing Ap. However, only half of the neurons born from neuroblasts at other transcription factor stages maintain expression of the neuroblast transcription factor, e.g., in the progeny of Ey+ neuroblasts, Ey+ neurons are intermingled with about an equal number of Ey− neurons that instead express Ap.
Left figure shows Ap salt-and-pepper manner expression (Notch lateral inhibition like). Note Su(H) is a effector of Notch pathway. The region with deficient Su(H) shows absent of Ap expression, indicating Ap is a downstream responser of Notch pathway. Right is a very clear diagram shows Hth is the only case where both daughter cells express Hth itself, while other tTF only enjoy half of it progeny to inherit its tTF identity (rest half of it are taken by Ap).
These data suggest that, for Ey+ or Slp+ GMCs, the Notch-OFF daughter maintains the neuroblast transcription factor expression, whereas the Notch-ON daughter loses this expression but expresses Ap.
