Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice.

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex.

PICK1 expression in reactive astrocytes within the spinal cord of amyotrophic lateral sclerosis (ALS) rats.

AIMS: The protein interacting with C kinase 1 (PICK1), a PDZ domain-containing protein mainly expressed in the central nervous system, interacts with the glutamate receptor subunit GluR2, with the glutamate transporter GLT-1b and with the enzyme serine racemase. These three proteins appear as key actors in the glutamate-mediated excitotoxicity associated with amyotrophic lateral sclerosis (ALS), in both patients and animal models of the disease. In this study, we examined the expression of PICK1 in the spinal cord of transgenic rats expressing a mutated form of the human superoxide dismutase 1 (hSOD1(G93A) ) during the progression of the disease. METHODS: Expression of PICK1 was examined by real-time qPCR at presymptomatic and symptomatic stages as well as at end-stage. The expression of PICK1 in the different cell types of the spinal cord was examined by immunohistochemistry. RESULTS: The overall expression of PICK1 is not modified in cervical and lumbar spinal cord of transgenic (hSOD1(G93A) ) rats during the progression of the disease. Nonetheless, immunohistochemical studies of lumbar ventral horns revealed a shift of PICK1 expression from motor neurones in healthy rats to activated astrocytes in end-stage hSOD1(G93A) animals. CONCLUSIONS: Considering the documented influence of PICK1 expression on d-serine release and glutamate transport in astrocytes, these findings point to a potential implication of PICK1 in the progression of ALS.