Expression patterns of the hepatic leukemia factor gene in the nervous system of developing and adult mice

Abstract

Hepatic leukemia factor (HLF) is a bZIP transcription factor related to the CES-2 protein, which controls apoptosis of the NSM serotoninergic neurons in Caenorhabditis elegans. Ectopic expression of HLF as an E2A-HLF fusion protein in t(17;19)-positive human pro-B cell acute lymphoblastic leukemias is believed to promote malignancy by interfering with apoptosis. While HLF has been linked to malignancies of the lymphoid system, it is not normally expressed in these cells. Rather, HLF transcripts are detected in the liver, kidney, lung and adult nervous system by Northern blotting. Despite the links to cell death, little is known of the distribution or function of HLF in the adult and developing mammalian nervous system. Therefore, we cloned mouse Hlf and studied its expression by in situ hybridization. During embryonic brain development, Hlf expression was restricted to the anterior pituitary and meninges. By early postnatal life, Hlf was highly expressed in somatosensory cortex, thalamic nuclei, and structures arising from ectodermal placodes. Subsequently, Hlf expression increased in the central nervous system and was found throughout the brain by adulthood. In the developing pituitary gland, Hlf was highly expressed in the rostral tip of the anterior lobe. This pattern is similar to that of Tef, an Hlf-related bZIP protein. However, while Tef is expressed in the anterior pituitary of the adult mouse, Hlf was detected in both the anterior and posterior pituitary. Hlf expression was not associated with cells undergoing programmed cell death in the nervous system. Hlf expression increased markedly with synaptogenesis and was coincident with barrel formation revealed by cytochrome oxidase staining. Together, these data suggest that Hlf plays a role in the function of differentiated neurons in the adult nervous system rather than programmed cell death.