Lateral inhibition via As-c signaling generates a neuroblast
Notch activation leads to suppression of neural gene expression
Enhancer of split
asc
N, Dl both
on; As-c
low
N off/Asc high;
N on/Dl off/
Asc off
A close-up of Notch signaling (in non-neuroblast cells)
FEBS Lett 580(12): 2860–2868
The initial N vs. Dl imbalance is amplified by two TFs, Su(H) &
E(spl)
The neural fate of embryonic ectodermal cells is suppressed
by neuroblasts
Proneural cell clusters initially express achaete-scute
… then the clusters become refined to 1 As-c+ NB
Gain-of-function Notch mutation: more neuroblasts
Loss-of-function Notch mutation: premature neurons, less NBs
bHLH transcription factors & cell fate determination
The As-c genes drive lateral inhibition via Notch signaling in
ectoderm
As-c and Notch-Delta mutations give opposite phenotypes
Injecting activated Notch into one blastomere inhibits
neuroblast proliferation; inhibiting Delta causes excessive
neuronal
specification
L: sensory neurons
I: interneurons
M: motor neurons
Precocious Notch:
Loss of progenitors
Loss of Notch signaling:
Too many neuroblasts/
neurons
Notch signaling influences neuron vs. glia development
Hes1: neural gene inhibitor
The proneural genes and the Notch pathway regulate neurogenesis. A. As described in Chapter 1, the
proneural genes are important in the initial segregation of neural tissue from the epidermis in both
Drosophila and vertebrates and function through an inter-cellular feedback loop to amplify small biases
between cells. Proneural transcription factors induce expression of Notch ligands (DL) which then
activate the Notch receptor in adjacent cells (N) to drive Hes1 expression, which inhibits the proneural
genes. B. Within the progenitor population in the ventricular zone, all the cells express these genes at
some level. Those cells that express higher levels differentiate as neurons (red).
Position of homeobox genes on the chromosomes correlates with their
regional expression pattern
The Hoxb1 genetic locus: 5’ & 3’ RAREs, Hoxa1, repressors &
enhancers
from Marshall et al,
FASEB J 1996; 10:
969-978
Labeled nucleotides can be used to identify cells in S phase
BrdU: S phase label, phospho-histone H3: M phase label
Neural progenitors divide asymmetrically to form neurons
Peak-to-peak labeling of M phase cells = cycle length
Neuronal migration during cerebellar development
Cerebellum: two progenitor zones, granule cells vs. Purkinje
Rodents generate new olfactory neurons throughout life
Lineage tracing to follow cell fate and migration
Cortical interneurons derive from ventral forebrain (LGE)
Interneurons migrate tangentially; other neurons migrate radially
Neurons are also born in adult hippocampus (dentate gyrus)
Neurogenesis begins with a simple tube…
Cerebral cortex morphogenesis in 3 stages: VZ  PP/SP 
Cortical plate
Cerebral cortical layers are formed inside-out
Primate corticogenesis: 50-day process (rodent: ~14 days)