EARLY ONTOGENY OF CATECHOLAMINERGIC CELL LINEAGE IN BRAIN AND PERIPHERAL NEURONS MONITORED BY TYROSINE HYDROXYLASE-LACZ TRANSGENE

As the first and rate limiting enzyme in the biosynthetic pathway for catecholamine (CA) neurotransmitters, tyrosine hydroxylase (TH) is a s pecific phenotypic marker for CA cells in the central and peripheral n ervous systems of adult animals. During embryogenesis, TH expression a ppears permanently within cells destined to be CA-secreting during adu lt life, and transiently in several cell types that will not express T H in adulthood. In this study, we examined the early ontogeny of TH ex pression in transgenic mouse embryos by following the expression of a lacZ reporter, driven by the tissue-specific promoter of the rat TH ge ne. The lacZ reporter product, beta-galactosidase (beta-gal), visualiz ed by X-gal staining, first became apparent in primordia of sensory ga nglia serving the glossopharyngeal (IX) and vagal (X) cranial nerves a t embryonic day (E)9.0. Between E9.5 and E10.5, beta-gal expression ex tended to the remaining cranial sensory ganglia serving the trigeminal (V) and facial (VII) nerves, dorsal root ganglia, ventrolateral neura l tube and sympathetic ganglion primordia. During that same period, th e first beta-gal expression in the embryonic brain also appeared withi n distinct regions, such as the ventral prosencephalon, the ventral an d dorsolateral mesencephalon and the rostral and caudal rhombencephalo n. The level of beta-gal expression in all these tissues decreased at E13.5, but a distinct adult pattern of beta-gal expression started to emerge in the substantia nigra and ventral tegmental area in the centr al nervous system and the adrenal medulla in the periphery. Our findin gs indicate that the proximal 9.0 kb of the 5' promoter region of the rat TH gene encodes sufficient information to direct development of th e appropriate catecholaminergic lineage cells in the central and most peripheral nervous systems during embryogenesis.