Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The lateral line microcosmos Alain Ghysen1 and Christine Dambly-Chaudière Laboratory of Neurogenetics Institut National de la Sante´et de la Recherche Me´dicale (INSERM) U881, 34095 Montpellier, France The lateral-line system is a simple sensory system com- This sensory system is involved in a large repertoire of prising a number of discrete sense organs, the neuro- behaviors, e.g., swimming against current, prey detec- masts, distributed over the body of fish and amphibians tion and/or predator avoidance, social behaviors such as in species-specific patterns. Its development involves schooling, and sexual courtship (Coombs and Montgom- fundamental biological processes such as long-range cell ery 1999). The idea of a “distant-touch” sensory system migration, planar cell polarity, regeneration, and post- has been explored in the context of improving underwa- embryonic remodeling. These aspects have been exten- ter safety for human devices, and an artificial lateral line sively studied in amphibians by experimental embryolo- has been developed (Yang et al. 2006) that shows an gists, but it is only recently that the genetic bases of this amazing capability to analyze movements of nearby bod- development have been explored in zebrafish. This re- ies and wake signatures (water eddies). view discusses progress made over the past few years in The lateral-line system comprises two major branches, this field. an anterior part that extends on the head, and a posterior part that extends on the trunk and tail. The development of the posterior lateral-line system (PLL) has been stud- Souvienne vous de celui à qui, comme on demandait à ied in amphibians and was shown to involve the forma- quoi faire il se peinait si fort en un art qui ne pouvait tion of a migrating primordium that deposits small venir à la connaissance de guère de gens: J’en ai assez groups of cells, each one a prospective neuromast, in its de peu, répondit-il, j’en ai assez d’un, j’en ai assez de wake (Harrison 1904). A migrating primordium was later pas un. demonstrated to initiate the development of the PLL in Michel de Montaigne, Essais, Livre I, Chap. XXXVIII zebrafish, as well (Metcalfe et al. 1985). Most of the re- (1595) cent work refers to the posterior lateral-line system; the (Remember the person who, when he was asked why development of the anterior lateral-line system, which he was working so hard on something that would extends on the head, has not been much analyzed so far. come to the attention of scarcely anyone: I will be However, it certainly differs from the posterior system in satisfied with a few, he answered, I will be satisfied many respects, not the least of which is its independence with one, I will be satisfied with no one.) on the molecules that drive migration of the posterior system. The lateral-line system of fish and amphibians com- The potential of the PLL to shed light on important prises a set of discrete sensory organs and the neurons developmental mechanisms, because of its structural that innervate them. Both electrosensory and mechano- simplicity and experimental accessibility, has recently sensory organs are present in many fish species, but only been recognized (for review, see Ghysen and Dambly- mechanosensory organs (neuromasts) are present in ze- Chaudière 2004). In this review we will focus on several brafish. At the core of each neuromast is a group of sen- aspects of lateral line development that have made con- sory hair cells that respond to the deflection of their siderable progress over the past 2 to 3 yr. Our aim is to cilia. Neuromasts therefore provide information about give an overview of the perspectives that have been the local water flow. The system was discovered more opened by this recent work, in relation to a small num- than a century ago (for review, see Dijkgraaf 1989) and ber of fundamental biological questions such as long- was long assigned an auditory function, mostly because range cell migration, planar cell polarity, regeneration, its mechanosensory hair cells are very similar to those of and size control. This has led us to mention and discuss the inner ear. The current view, however, is that the ideas and models that still lack rigorous demonstration, lateral-line system mediates a sense of “touch-at-a-dis- because we believe that the present strength of the sys- tance” (Dijkgraaf 1963). tem is precisely to provoke ideas and invite thought. Background: development of the zebrafish PLL [Keywords: Lateral line; hair cells; zebrafish; cell migration; regeneration; planar cell polarity] The PLL originates as a placode that forms just posterior 1Corresponding author. E-MAIL [email protected]; FAX 33-4-67143928. to the otic vesicle. The mechanisms involved in the in- Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1568407. duction of lateral-line placodes have been extensively 2118 GENES & DEVELOPMENT 21:2118–2130 © 2007 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/07; www.genesdev.org Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press The lateral line microcosmos reviewed recently and will not be dealt with here (Baker Haas and Gilmour 2006). Upon reaching the tip of the and Bronner-Fraser 2001; Schlosser 2002a,b; see also tail, the primordium fragments and forms two to three Schlosser 2006). In zebrafish, the PLL placode delami- terminal neuromasts (Fig. 1B). A few hours after deposi- nates at 18–20 h post-fertilization (hpf) by a still poorly tion, each proneuromast differentiates into a functional understood process (Kimmel et al. 1995). It rapidly di- neuromast (Fig. 1E, inset). A mature neuromast com- vides into a small anterior compartment of ∼20 cells that prises a core of 15–20 mechanosensory hair cells sur- differentiate as sensory neurons and form the PLL gan- rounded by two types of accessory cells: the support cells glion, and a large compartment of ∼100 cells, the PLL and the mantle cells. The support cells underlie and sur- primordium. At 20 hpf, the primordium begins to mi- round the hair cells, and are themselves surrounded by grate caudally at a speed of ∼150 µm/h (Fig. 1A), and the mantle cells, which line the neuromast (Hernandez reaches the tip of the tail at ∼40 hpf. As the primordium et al. 2007). The kinocilia of the hair cells are embedded migrates, it is accompanied by axons extending from the in a cupula thought to be secreted by the mantle cells. ganglion (Metcalfe 1985; Gilmour et al. 2004). Glial cells A second primordium, primII, arises at about the time in turn migrate along the axons (Gilmour et al. 2002) to the first primordium (primI) has reached the tip of the form the myelinated PLL nerve (Brösamle and Halpern tail (Fig. 1B; Sapède et al. 2002). PrimII is smaller and 2002) slower than primI, and takes almost a week to reach the The migrating primordium deposits five groups of ∼20 level of the anus, about halfway between the head and cells, the proneuromasts, in its wake (Fig. 1B). Deposi- the tip of the tail. A dorsal line forms at the same time tion results from a concerted slowing down of the cells at (Fig. 1B). Additional neuromasts are progressively added the trailing edge of the primordium (Gompel et al. 2001; to both lines (Fig. 1C), and the line of lateral neuromasts Figure 1. Development of the posterior lateral-line system (PLL). (A) At 32 hpf, the migrating primordium is about halfway in its journey to the tip of the tail. It has deposited two neuromasts, L1 and L2, as well as a thin stream on interneuromastic cells (red). (B) At 3 d, primI has reached the tip of the tail where it fragments to form two to three terminal neuromasts (red). A second primordium forms ∼36 hpf and splits to form primII, which follows the same path as primI along the horizontal myoseptum, and primD, which initiates the dorsal line (blue). (C) At 3 wk, intercalary neuromasts are formed by the interneuromastic cells deposited by primI (red). At this time, primD and primII have completed their journey (blue). The dorsal line never extends beyond the dorsal fin. The lateral neuromasts are shifting to more ventral positions. (D) At the larval–juvenile transition, the lateral and dorsal lines are complete and are shifted ventrally. Two new lines have formed at the original positions at the embryonic lines: one along the horizontal myoseptum and one along the dorsal midline (light green). (E) Young adult fish exposed to a fluorescent vital dye specific for hair cells. All individual neuromasts of the juvenile have given rise to dorso-ventrally aligned clusters of neuromasts (stitches). Stitches continue to expand during the entire life of the fish. (Inset) 48-hpf embryo at the same scale as the adult. Scale bars, 1 mm. GENES & DEVELOPMENT 2119 Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Ghysen and Dambly-Chaudière derived from primI and primII migrates ventrally (Fig. 1C; Ledent 2002). Thus, at ∼2–3 wk, the larval PLL com- prises two lines of neuromasts, a ventral one that in- cludes neuromasts deposited by primI and primII, and a dorsal one (Fig. 1C). Over the following several weeks, the neuromasts of the dorsal line also migrate ventrally, and two new lines of neuromasts form at the same lateral and dorsal positions where the embryonic lines first appeared (Fig. 1D, green dots). In a final step of am- plification, each neuromast gives rise to dorso-ventrally elongated clusters of neuromasts called “stitches” (Fig.