Published August 15, 2022 - More info
The olfactory bulb (OB) receives odor information from the olfactory epithelium and relays this to the olfactory cortex. Using a mouse model, we found that development and maturation of OB interneurons depends on the zinc finger homeodomain factor teashirt zinc finger family member 1 (TSHZ1). In mice lacking TSHZ1, neuroblasts exhibited a normal tangential migration to the OB; however, upon arrival to the OB, the neuroblasts were distributed aberrantly within the radial dimension, and many immature neuroblasts failed to exit the rostral migratory stream. Conditional deletion of Tshz1 in mice resulted in OB hypoplasia and severe olfactory deficits. We therefore investigated olfaction in human subjects from families with congenital aural atresia that were heterozygous for TSHZ1 loss-of-function mutations. These individuals displayed hyposmia, which is characterized by impaired odor discrimination and reduced olfactory sensitivity. Microarray analysis, in situ hybridization, and ChIP revealed that TSHZ1 bound to and regulated expression of the gene encoding prokineticin receptor 2 (PROKR2), a G protein–coupled receptor essential for OB development. Mutations in PROKR2 lead to Kallmann syndrome, characterized by anosmia and hypogonadotrophic hypogonadism. Our data indicate that TSHZ1 is a key regulator of mammalian OB development and function and controls the expression of molecules involved in human Kallmann syndrome.
Daniela Ragancokova, Elena Rocca, Anne M.M. Oonk, Herbert Schulz, Elvira Rohde, Jan Bednarsch, Ilse Feenstra, Ronald J.E. Pennings, Hagen Wende, Alistair N. Garratt
Original citation: J Clin Invest. 2014;124(3):1214–1227. https://doi.org/10.1172/JCI72466
Citation for this corrigendum: J Clin Invest. 2022;132(16):e163087. https://doi.org/10.1172/JCI163087
The description of the primers for ChIP and the size of the Prokr2 PCR fragment were incorrect in the Methods. The correct text is below.
We showed results for 2 sets of primers: promoter (5′-CACACTCCAACTCTGCACACTTAGT-3′ and 5′-ACTGAATTAGGGTCTCAGACTTCCG-3′; 154 bp), which served as a negative control for binding in the promoter sequence, and intron 1 (5′-TTCAGGGCCATTTCAAGCACGGCTA-3′ and 5′- ATACCCTCTTCTGGCCTCAGACAGT-3′; 235 bp), which served to detect a putative binding site of TSHZ1 in the first intron of Prokr2.
In addition, we have corrected errors in the text in the legend of Supplemental Figure 1C and in the Supplemental Methods in the description of the generation of mice.
The authors regret the errors.
See the related article at TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction.