Class Distinction Neurons Through the Specification of Class B Progenitors

HIGHLIGHTS

DEVELOPMENT causes class A progenitors to adopt a class B fate. The authors conclude that Lbx1 is required for the generation of dorsal association inter- Class distinction neurons through the specification of class B progenitors. In the developing spinal cord, the dorsal neural The authors also gained an insight into when tube gives rise to two populations of somato- Lbx1 acts during neurogenesis. Lbx1 expression sensory interneurons — association and relay appears in class B cells only after they have left neurons. Little is known about the factors that the proliferative ventricular zone, indicating specify these different neuronal subtypes, that it acts on postmitotic neurons. This implies but two groups now report in Neuron that that neuronal progenitor cells in the dorsal the transcription factor Lbx1 seems to have an spinal cord retain some developmental plastic- important role. ity after they have stopped dividing, and that Two classes of neuronal progenitors, which their fate can be altered by manipulating the Müller et al. designate as class A and class B, expression of Lbx1. emerge from the dorsal spinal cord. The class A It has been known for some time that the cells are initially positioned dorsal to the class B dorsal neural tube consists of several progeni- cells, although the two populations swap posi- tor domains, each of which expresses a dis- tions later in development. The class A cells, tinct combination of transcription factors. which do not express Lbx1, give rise to relay However, Lbx1 is the first factor to be assigned interneurons. The class B cells, which express a specific role in the specification of dorsal Lbx1, give rise to association interneurons that neuronal subtypes. go on to colonize the substantia gelatinosa. Heather Wood Gross et al. and Müller et al. used loss- and References and links gain-of-function approaches to examine the ORIGINAL RESEARCH PAPER Gross, M. K. et al. Lbx1 role of Lbx1 in dorsal interneuron specifica- specifies somatosensory association interneurons in the dorsal spinal cord. Neuron 34, 535–549 (2002) | Müller, T. et al. The tion. They found that knocking out the Lbx1 homeodomain factor Lbx1 distinguishes two major programs of gene causes respecification of the class B cells to neuronal differentiation in the dorsal spinal cord. Neuron 34, a class A identity, which is manifested in a loss 551–562 (2002) WEB SITES of dorsal horn association interneurons. Encyclopedia of Life Sciences: http://www.els.net/ Misexpression of Lbx1, on the other hand, neuronal subtype identity regulation

CELL BIOLOGY OF THE NEURON

Curling the curl in coincidence detection Metabotropic Ca2+ receptor channel The inositol-1,4,5-trisphosphate led to channel opening in the absence of

(Ins(1,4,5)P3) receptor (InsP3R) is a calcium Ins(1,4,5)P3, indicating that CaBPs can act as channel of the endoplasmic reticulum. It is ligands of this receptor. They also showed well known that this channel opens in co-localization of CaBPs and the InsP3R, and response to Ins(1,4,5)P3 and calcium, but new obtained evidence that the two proteins Ca2+ data indicate that signalling through this interact in brain lysates. Ca2+ pathway might be more complex than we InsP3R channel opening requires both previously thought; Yang et al. have identified Ins(1,4,5)P3 and calcium. For this reason, this a family of proteins that can directly activate molecule has been thought of as a coincidence the channel in the absence of Ins(1,4,5)P3. detector that can sense the activation of The authors looked for proteins that bind separate synaptic inputs that might + + Ins(1,4,5)P3 InsP3R CaBP to the InsP3R and singled out a group of independently increase the levels of those two molecules that are known as calcium-binding small signalling molecules. The data of Yang proteins (CaBPs). CaBPs belong to a larger et al. complicate this view because they raise Endoplasmic family of proteins known as neuronal the possibility that the InsP3R is activated reticulum calcium-binding proteins, which includes simply as the result of an elevation in calcium. molecules such as recoverin, frequenin and As coincidence detection by the InsP3R has calsenilin.Yang et al. found that CaBPs been invoked, in particular, to explain interact with the three different isoforms of cerebellar long-term depression, Purkinje References and links the InsP R, and that the interaction depends cells might be a good system in which to ORIGINAL RESEARCH PAPER Yang, J. et al. Identification 3 of a family of calcium sensors as protein ligands of inositol on the ability of the CaBPs to bind calcium. explore the implications of the new findings. trisphosphate receptor Ca2+ release channels. Proc. Natl Acad. Sci. USA 99, 7711–7716 (2002) Crucially, binding of the CaBPs to the InsP3R Juan Carlos López

490 | JULY 2002 | VOLUME 3 www.nature.com/reviews/neuro