haploinsufficiency causes brain abnormalities with functional relevance.

Introduction: The Notch pathway is fundamental for the generation of neurons during development. We previously reported that adult mice heterozygous for the null allele of the gene encoding the Delta-like ligand 1 for Notch ( ) have a reduced neuronal density in the substantia nigra pars compacta. The aim of the present work was to evaluate whether this alteration extends to other brain structures and the behavioral consequences of affected subjects.

The Substantia Nigra Is Permissive and Gains Inductive Signals When Lesioned for Dopaminergic Differentiation of Embryonic Stem Cells.

Transplantation of dopaminergic (DA) cells into the striatum can rescue from dopamine deficiency in a Parkinson's disease condition, but this is not a suitable procedure for regaining the full control of motor activity. The minimal condition toward recovering the nigrostriatal pathway is the proper innervation of transplanted DA neurons or their precursors from the substancia nigra pars compacta (SNpc) to their target areas. However, functional integration of transplanted cells would require first that the host SNpc is suitable for their survival and/or differentiation.

Functional determination of the differentiation potential of ventral mesencephalic neural precursor cells during dopaminergic neurogenesis.

The ventral mesencephalic neural precursor cells (vmNPCs) that give rise to dopaminergic (DA) neurons have been identified by the expression of distinct genes (e.g., Lmx1a, Foxa2, Msx1/2).

Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain.

Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs), but plays an important role in regulating their expansion and differentiation into neurons.

Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain.

A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether "silent" neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo.

Telencephalic neural precursor cells show transient competence to interpret the dopaminergic niche of the embryonic midbrain.

Neural Precursor Cells (NPCs) generate complex stereotypic arrays of neuronal subtypes in the brain. This process involves the integration of patterning cues that progressively restrict the fate of specific NPCs. Yet the capacity of NPCs to interpret foreign microenvironments during development remains poorly defined.