FGF-dependent midline-derived progenitor cells in hypothalamic infundibular development.

The infundibulum links the nervous and endocrine systems, serving as a crucial integrating centre for body homeostasis. Here we describe that the chick infundibulum derives from two subsets of anterior ventral midline cells. One set remains at the ventral midline and forms the posterior-ventral infundibulum. A second set migrates laterally, forming a collar around the midline. We show that collar cells are composed of Fgf3(+) SOX3(+) proliferating progenitors, the induction of which is SHH dependent, but the maintenance of which requires FGF signalling. Collar cells proliferate late into embryogenesis, can generate neurospheres that passage extensively, and differentiate to distinct fates, including hypothalamic neuronal fates and Fgf10(+) anterior-dorsal infundibular cells. Together, our study shows that a subset of anterior floor plate-like cells gives rise to Fgf3(+) SOX3(+) progenitor cells, demonstrates a dual origin of infundibular cells and reveals a crucial role for FGF signalling in governing extended infundibular growth.

Up-regulation of fibroblast growth factor 3 is associated with tumor metastasis and recurrence in human hepatocellular carcinoma.

Recently, we established a hepatocellular carcinoma (HCC) cell line (named H4-M) from a metastatic HCC tumor. In H4-M, a marker chromosome containing a homogeneously staining region (hsr) was identified by cytogenetic analysis. The hsr was characterized by chromosome microdissection and the result showed that the hsr was composed of DNA sequence from 11q13. Oncogenes CCND1 and FGF3 were localized within the complicon and overexpressions of CCND1 and FGF3 were confirmed by Northern blot analysis. Clinical significance of FGF3 overexpression was studied by immunohistochemistry (IHC) using an HCC tissue microarray (TMA) containing 60 pairs of primary/metastatic HCCs and 30 pairs of primary/recurrent HCCs. TMA study showed that overexpression of FGF3 was significantly associated with HCC metastasis and recurrence (p<0.01), suggesting that up-regulation of FGF3 may play an important role in HCC metastasis and recurrence.

Zebrafish pax5 regulates development of the utricular macula and vestibular function.

The zebrafish otic vesicle initially forms with only two sensory epithelia, the utricular and saccular maculae, which primarily mediate vestibular and auditory function, respectively. Here, we test the role of pax5, which is preferentially expressed in the utricular macula. Morpholino knockdown of pax5 disrupts vestibular function but not hearing. Neurons of the statoacoustic ganglion (SAG) develop normally. Utricular hair cells appear to form normally but a variable number subsequently undergo apoptosis and are extruded from the otic vesicle. Dendrites of the SAG persist in the utricle but become disorganized after hair cell loss. Hair cells in the saccule develop and survive normally. Otic expression of pax5 requires pax2a and fgf3, mutations in which cause vestibular defects, albeit by distinct mechanisms. Thus, pax5 works in conjunction with fgf3 and pax2a to establish and/or maintain the utricular macula and is essential for vestibular function.