Abstract
Background:
During retinal and spinal cord neurogenesis, Notch signaling plays crucial roles in regulating proliferation and differentiation of progenitor cells. One of the Notch ligands, Delta-like 4 (Dll4), has been shown to be expressed in subsets of retinal and spinal cord progenitors/precursors and involved in neuronal subtype specification. However, it remains to be determined whether Dll4 expression has any progenitor/precursor-specificity contributing to its functional specificity during neural development.
Results:
We generated a Dll4-Cre BAC transgenic mouse line that drives Cre recombinase expression mimicking that of the endogenous Dll4 in the developing retina and spinal cord. By fate-mapping analysis, we found that Dll4-expressing progenitors/precursors give rise to essentially all cone, amacrine and horizontal cells, a large portion of rod and ganglion cells, but only few bipolar and Müller cells. In the spinal cord, Dll4-expressing progenitors/precursors generate almost all V2a and V2c cells while producing only a fraction of the cells for other interneuron and motor neuron subtypes along the dorsoventral axis.
Conclusions:
Our data suggest that selective expression of Dll4 in progenitors/precursors contributes to its functional specificity in neuronal specification and that the Dll4-Cre line is a valuable tool for gene manipulation to study Notch signaling.
Keywords:
Dll4; Notch signaling; V2 interneuron; neuronal lineage; retina; spinal cord.