EXPRESSION OF GAP-43 (NEUROMODULIN) DURING THE DEVELOPMENT OF THE RATADRENAL-GLAND

The 'growth-associated protein', GAP-43 was originally considered to b e a neuron-specific protein associated with plasticity. However, we ha ve recently shown that GAP-43 is expressed by noradrenergic, but not b y adrenergic chromaffin cells in the adult rat adrenal gland. In this study, we examine the expression of GAP-43 during embryonic and post-n atal development of the adrenal gland using immunohistochemical techni ques. In parallel, antibodies directed against two neuroendocrine mark ers, the catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were employed to pe rmit identification of the developing chromaffin cell phenotypes. At e mbryonic day 15.5, GAP-43 was predominately localized in sympathoadren ergic precursor cells in the extra-adrenal blastema, and also in nerve fibers within the adrenal gland. At later embryonic stages, GAP-43 wa s expressed by nearly all intra-adrenal chromoblasts. Two subsets of c hromoblasts can be distinguished even at early stages. A strong GAP-43 -positive immunoreaction was observed in those chromoblasts organized in a few large compact clusters which weakly expressed TH and did not express PNMT. A generally weaker GAP-43 immunoreaction was observed in a second type of intra-adrenal chromoblasts which were organized in s mall isolated groups and characterized by a PNMT-positive, and strong TH-positive immunoreactivity. GAP-43 immunoreactivity was still associ ated with many PNMT-positive adrenergic chromoblasts at birth, but dec reased to undetectable levels during the first post-natal week. By the second post-natal week, GAP-43 was restricted, as in the adult, to no radrenergic chromaffin cells which expressed TH, but not PNMT, in addi tion to nerve fibers and their associated glial cells in the gland. An immunoblot analysis confirmed a decrease in GAP-43 protein during the post-natal period. In agreement with these observations, a three-fold decrease in GAP-43 mRNA in the adrenal gland was measured between lat e embryogenesis and the second post-natal week. During development, th e spatiotemporal expression of GAP-43 suggests a possible role in the migration and aggregation of chromaffin cell precursors into the medul lary region of the adrenal gland.