Neurogenic Potential Of Dental Pulp Stem Cells

E-mail address: sblack@jhmi.edu (S. Blackshaw). Lim homeodomain transcription factor 1 (Lhx1) is the first transcription factor that is selectively expressed in the developing hypothalamic suprachiasmatic nucleus (SCN), the body’s master clock. In the present study, we demonstrate that the Six3-Cre transgene is robustly active in developing SCN, and use this mouse line to selectively delete Lhx1 in SCN without affecting its expression in other brain regions. When analyzed by microarray and in situ hybridization, the SCN of Six3-Cre; Lhx1lox/lox mice demonstrated a profound loss of expression of Vip, Avp and Grp—neuropeptides which are involved both in synchronization of the cellular circadian oscillators of SCN neurons and in relay of circadian phase information to other brain regions. However, SCN-enriched transcripts whose expression is detectable prior to the end of neurogenesis at E16.5—such as Gad67, Rora, and Nr1d1 – showed little or no change in expression in mutant mice. Wheel-running behavior in these mice was slightly phase advanced but otherwise normal during a 12:12 light:dark (L:D) cycle, but became completely disorganized in both constant darkness and constant light, and were slow to re-entrain to 12:12 L:D. Moreover, unlike wild-type animals, mutant mice showed no overall differences in activity levels when maintained in constant darkness and constant light. Axonal projections of intrinsically photosensitive retinal ganglion cells to the SCN were unaffected in mutant animals, however. Our findings not only demonstrate a critical role for Lhx1 in terminal differentiation of SCN neurons, but also establish a novel genetic model in which SCN function is selectively disrupted without affecting the function of core cellular clock components.