N.A. and Brugmann, S.A. (2011). The emerging face of primary cilia. Genesis 49 (4): 231–246.72 Schock, E.N. and Brugmann, S.A. (2017). Discovery, diagnosis, and etiology of craniofacial ciliopathies. Cold Spring Harbor Perspect. Biol. 9 (9): 1–14.
73 Adel Al‐Lami, H., Barrell, W.B., and Liu, K.J. (2016). Micrognathia in mouse models of ciliopathies. Biochem. Soc. Trans. 44 (6): 1753–1759.
74 Marshall, W.F. (2008). The cell biological basis of ciliary disease. J. Cell Biol. 180 (1): 17–21.
75 Babbs, C., Furniss, D., Morriss‐Kay, G.M., and Wilkie, A.O. (2008). Polydactyly in the mouse mutant Doublefoot involves altered Gli3 processing and is caused by a large deletion in cis to Indian hedgehog. Mech. Dev. 125 (5–6): 517–526.
76 Haycraft, C.J., Banizs, B., Aydin‐Son, Y. et al. (2005). Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet. 1 (4): e53.
77 Rigueur, D. and Lyons, K.M. (2014). Whole‐mount skeletal staining. Methods Mol. Biol. 1130: 113–121.
78 Guemez‐Gamboa, A., Coufal, N.G., and Gleeson, J.G. (2014). Primary cilia in the developing and mature brain. Neuron 82 (3): 511–521.
79 Breunig, J.J., Sarkisian, M.R., Arellano, J.I. et al. (2008). Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc. Natl. Acad. Sci. U. S. A. 105 (35): 13127–13132.
80 Han, Y.G., Spassky, N., Romaguera‐Ros, M. et al. (2008). Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat. Neurosci. 11 (3): 277–284.
81 Spassky, N., Han, Y.G., Aguilar, A. et al. (2008). Primary cilia are required for cerebellar development and Shh‐dependent expansion of progenitor pool. Dev. Biol. 317 (1): 246–259.
82 Lee, J.E. and Gleeson, J.G. (2011). Cilia in the nervous system: linking cilia function and neurodevelopmental disorders. Curr. Opin. Neurol. 24 (2): 98–105.
83 Gressens, P. (2006). Pathogenesis of migration disorders. Curr. Opin. Neurol. 19 (2): 135–140.
84 Louie, C.M. and Gleeson, J.G. (2005). Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum. Mol. Genet. 14 (2): R235–R242.
85 Bashford, A.L. and Subramanian, V. (2019). Mice with a conditional deletion of Talpid3 (KIAA0586) – a model for Joubert syndrome. J. Pathol. 248 (4): 396–408.
86 Jones, C., Roper, V.C., Foucher, I. et al. (2008). Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat. Genet. 40 (1): 69–77.
87 Imtiaz, A., Belyantseva, I.A., Beirl, A.J. et al. (2018). CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum. Mol. Genet. 27 (5): 780–798.
88 McEwen, D.P., Jenkins, P.M., and Martens, J.R. (2008). Olfactory cilia: our direct neuronal connection to the external world. Curr. Top. Dev. Biol. 85: 333–370.
89 Jenkins, P.M., McEwen, D.P., and Martens, J.R. (2009). Olfactory cilia: linking sensory cilia function and human disease. Chem. Senses 34 (5): 451–464.
90 McIntyre, J.C., Davis, E.E., Joiner, A. et al. (2012). Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model. Nat. Med. 18 (9): 1423–1428.
91 Kulaga, H.M., Leitch, C.C., Eichers, E.R. et al. (2004). Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat. Genet. 36 (9): 994–998.
92 Acs, P., Bauer, P.O., Mayer, B. et al. (2015). A novel form of ciliopathy underlies hyperphagia and obesity in Ankrd26 knockout mice. Brain Struct. Funct. 220 (3): 1511–1528.
93 Vaisse, C., Reiter, J.F., and Berbari, N.F. (2017). Cilia and obesity. Cold Spring Harbor Perspect. Biol. 9 (7): 1–13.
94 Mukhopadhyay, S. and Jackson, P.K. (2013). Cilia, tubby mice, and obesity. Cilia 2: 1.
95 Stratigopoulos, G., Burnett, L.C., Rausch, R. et al. (2016). Hypomorphism of Fto and Rpgrip1l causes obesity in mice. J. Clin. Invest. 126 (5): 1897–1910.
96 Khanna, H., Davis, E.E., Murga‐Zamalloa, C.A. et al. (2009). A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat. Genet. 41 (6): 739–745.
97 Louie, C.M., Caridi, G., Lopes, V.S. et al. (2010). AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat. Genet. 42 (2): 175–180.
98 Rachel, R.A., May‐Simera, H.L., Veleri, S. et al. (2012). Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis. J. Clin. Invest. 122 (4): 1233–1245.
99 Gattone, V.H. 2nd, MacNaughton, K.A., and Kraybill, A.L. (1996). Murine autosomal recessive polycystic kidney disease with multiorgan involvement induced by the cpk gene. Anat. Rec. 245 (3): 488–499.
100 Ricker, J.L., Gattone, V.H. 2nd, Calvet, J.P., and Rankin, C.A. (2000). Development of autosomal recessive polycystic kidney disease in BALB/c‐cpk/cpk mice. J. Am. Soc. Nephrol. 11 (10): 1837–1847.
101 Cook, S.A., Collin, G.B., Bronson, R.T. et al. (2009). A mouse model for Meckel syndrome type 3. J. Am. Soc. Nephrol. 20 (4): 753–764.
102 Zaki, M.S., Sattar, S., Massoudi, R.A., and Gleeson, J.G. (2011). Co‐occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers. Am. J. Med. Genet. Part A 155A (12): 3042–3049.
103 Wolf, M.T. and Hildebrandt, F. (2011). Nephronophthisis. Pediatr Nephrol. 26 (2): 181–194.
104 Beales, P.L., Badano, J.L., Ross, A.J. et al. (2003). Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non‐Mendelian Bardet–Biedl syndrome. Am. J. Hum. Genet. 72 (5): 1187–1199.
105 Hildebrandt, F., Benzing, T., and Katsanis, N. (2011). Ciliopathies. N. Engl. J. Med. 364 (16): 1533–1543.
106 Chaki, M., Hoefele, J., Allen, S.J. et al. (2011). Genotype–phenotype correlation in 440 patients with NPHP‐related ciliopathies. Kidney Int. 80 (11): 1239–1245.
7 Hematopoietic and Lymphoid Tissues
Harm HogenEsch and John P. Sundberg
Introduction
Hematopoiesis refers to the production of erythrocytes, leukocytes, and platelets from hematopoietic stem cells (HSCs), a population of self‐renewing cells that can give rise to all blood cell lineages. HSCs are needed throughout the life of mice to maintain blood cell populations because of their relatively short lifespan. HSCs are found in the bone marrow and spleen of adult mice and can be recruited to other extramedullary tissues when there is increased demand for hematopoiesis.
The hemopoietic system is derived from the mesoderm in three waves during embryonal development. The first and second waves occur in the yolk sac of the embryo beginning at embryonal day (ED) 7, and generate blood cells that supply the developing embryo including macrophages involved in tissue remodeling [1]. The definitive HSCs, which can reconstitute the entire hematopoietic
